Anaerobic Manufacturing and Molecular Analytical Process Optimization to Support Clinical Development of Live Biotherapeutic Products

厌氧制造和分子分析过程优化支持活生物治疗产品的临床开发

基本信息

批准号：
10482472
负责人：
Ricardo Valladares
金额：
$ 97.91万
依托单位：
SIOLTA THERAPEUTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-04 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10482472
关键词：
Acute Allergens Allergic Allergic Disease Allergic inflammation Anaerobic Bacteria Anaphylaxis Antioxidants Asthma Atopic Dermatitis Bacteria Biochemical Pathway Biological Markers Biological Response Modifier Therapy Bioreactors Cells Child Childhood Chronic Clinical Clinical Research Clinical Trials Cyclic GMP Data Set Desiccation Development Disease Disease model Economic Burden Environmental Risk Factor Eosinophilia Evaluation Excipients Extrinsic asthma Feces Flow Cytometry Food Hypersensitivity Formulation Freeze Drying Freezing Goals Healthcare Human Hypersensitivity IgE Immediate hypersensitivity Immune Immune Tolerance Immunologics Impairment Individual Infant Infiltration Interleukin-4 Intervention Lactobacillus Licensing Life Link Lung Lymph Mediating Metagenomics Methods Microbe Molecular Morbidity - disease rate Onset of illness Oral Pharmaceutical Preparations Pharmacologic Substance Phase Phase I Clinical Trials Phase II Clinical Trials Powder dose form Prevention Primary Prevention Probiotics Process Production Public Health Quality of life Reaction Recovery Regulatory T-Lymphocyte Reporting Risk Secondary Prevention Supplementation Symptoms System Temperature Testing Th2 Cells Therapeutic Training United States Food and Drug Administration Update Validation Work allergic airway inflammation analytical method base capsule clinical development clinical efficacy clinical material commensal bacteria commercialization cost design disorder prevention disorder risk global health gut microbiota immunoregulation improved in vivo innovation liquid formulation member method development microbial mouse model novel novel strategies potency testing pre-clinical prevent process optimization product development programs standard of care success therapeutic candidate

项目摘要

ABSTRACT Allergic diseases including atopic dermatitis, food allergy, and allergic asthma represent a global health problem that disproportionately impacts children. Surprisingly, there are no approved approaches to prevent the development of these diseases in at-risk individuals, resulting in chronic morbidity and economic burden. The management of asthma, for example, carries a steep cost burden of billions of dollars per year in the US alone, of which nearly 20 billion is spent on standard of care treatments with variable efficacy. Food allergy management is generally limited to allergen avoidance and rescue from severe acute anaphylaxis. There is a crucial need to develop innovative strategies to prevent the onset of these Type 1 allergic diseases rather than treating their symptoms. A preventative approach targeting at-risk individuals could significantly reduce the morbidity and healthcare burden associated with these increasingly common conditions. Studies confirm the link between gut microbiota development, immunological training, and allergic disease onset in childhood, and it is now clear that allergic disease risk is associated with aberrant microbial exposures over the first year of life. Longitudinal gut microbiota profiling studies in infants and children show that a loss of specific immunomodulatory commensal bacteria, and their metabolic networks, precedes allergic disease development. Using infant gut microbiota data sets and in vivo allergic disease models, Siolta Therapeutics has designed a live biotherapeutic product (LBP), STMC-103H, to stimulate tolerant immunological development and prevent allergic disease onset in at-risk individuals. STMC-103H contains three distinct active ingredient bacteria isolated from healthy human stool. Siolta has performed extensive cGMP manufacturing development, including formulation, process, and analytical method development, to support Phase 1 and Phase 2 clinical trials of STMC-103H under an IND with the FDA. In this project, we will build on our previous STMC-103H drug product development to improve the stability, potency, and characterization approaches for late-stage clinical trials and subsequent commercialization. Success of this project will directly support the regulatory and commercial development of STMC-103H. Indirectly, this work will improve the manufacturing and clinical development of diverse candidate LBPs containing sensitive live bacteria with high therapeutic potential. Siolta will also seek to license novel manufacturing approaches to other LBP developers.

抽象的过敏性疾病，包括特应性皮炎、食物过敏和过敏性哮喘，是一个全球性的健康问题这对儿童的影响尤为严重。令人惊讶的是，没有经过批准的方法来防止这些疾病在高危人群中发生，导致慢性发病率和经济负担。这例如，仅在美国，哮喘的治疗每年就承担数十亿美元的沉重成本负担，其中近 200 亿美元用于疗效参差不齐的标准护理治疗。食物过敏管理通常仅限于避免过敏原和挽救严重急性过敏反应。迫切需要制定创新策略来预防这些 1 型过敏性疾病的发生，而不是治疗它们症状。针对高危人群的预防方法可以显着降低发病率和与这些日益常见的疾病相关的医疗负担。研究证实肠道微生物群发育、免疫训练和过敏性疾病发病之间的联系在儿童时期，现在已经清楚，过敏性疾病风险与超过一年的异常微生物暴露有关生命的第一年。婴儿和儿童的纵向肠道微生物群分析研究表明，特定肠道菌群的丧失免疫调节共生细菌及其代谢网络先于过敏性疾病的发展。利用婴儿肠道微生物群数据集和体内过敏性疾病模型，Siolta Therapeutics 设计了一种活生物治疗产品 (LBP) STMC-103H，刺激耐受性免疫发育并预防高危人群中发生过敏性疾病。 STMC-103H 含有三种分离的不同活性成分细菌来自健康人类粪便。 Siolta 进行了广泛的 cGMP 制造开发，包括配方、工艺和分析方法开发，以支持 1 期和 2 期临床试验 STMC-103H 已获得 FDA 的 IND 批准。在这个项目中，我们将在之前的 STMC-103H 药品开发的基础上提高稳定性，后期临床试验和随后商业化的效力和表征方法。该项目的成功将直接支持STMC-103H的监管和商业开发。这项工作将间接改善多种候选 LBP 的制造和临床开发含有具有高治疗潜力的敏感活细菌。西奥尔塔还将寻求小说授权其他 LBP 开发商的制造方法。